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      Iron, Magnesium, Vitamin D, and Zinc Deficiencies in Children Presenting with Symptoms of Attention-Deficit/Hyperactivity Disorder

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      Author(s): 1 , * , 2
      Publication date (Electronic):
      Journal: Children
      Publisher: MDPI
      Keywords: attention-deficit/hyperactivity disorder, zinc, magnesium, vitamin D, ferritin, iron

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          Abstract

          Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder increasing in prevalence. Although there is limited evidence to support treating ADHD with mineral/vitamin supplements, research does exist showing that patients with ADHD may have reduced levels of vitamin D, zinc, ferritin, and magnesium. These nutrients have important roles in neurologic function, including involvement in neurotransmitter synthesis. The aim of this paper is to discuss the role of each of these nutrients in the brain, the possible altered levels of these nutrients in patients with ADHD, possible reasons for a differential level in children with ADHD, and safety and effect of supplementation. With this knowledge, clinicians may choose in certain patients at high risk of deficiency, to screen for possible deficiencies of magnesium, vitamin D, zinc, and iron by checking RBC-magnesium, 25-OH vitamin D, serum/plasma zinc, and ferritin. Although children with ADHD may be more likely to have lower levels of vitamin D, zinc, magnesium, and iron, it cannot be stated that these lower levels caused ADHD. However, supplementing areas of deficiency may be a safe and justified intervention.

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          Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.

          Darryl W. Eyles, Steven Smith, Robert Kinobe … (2005)
          Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1alpha-hydroxylase (1alpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain.
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            Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.

            Richard Allen, Daniel Picchietti, Wayne Hening … (2003)
            Restless legs syndrome is a common yet frequently undiagnosed sensorimotor disorder. In 1995, the International Restless Legs Syndrome Study Group developed standardized criteria for the diagnosis of restless legs syndrome. Since that time, additional scientific scrutiny and clinical experience have led to a better understanding of the condition. Modification of the criteria is now necessary to better reflect that increased body of knowledge, as well as to clarify slight confusion with the wording of the original criteria. The restless legs syndrome diagnostic criteria and epidemiology workshop at the National Institutes of Health. Members of the International Restless Legs Syndrome Study Group and authorities on epidemiology and the design of questionnaires and scales. To modify the current criteria for the diagnosis of restless legs syndrome, to develop new criteria for the diagnosis of restless legs syndrome in the cognitively impaired elderly and in children, to create standardized criteria for the identification of augmentation, and to establish consistent questions for use in epidemiology studies. The essential diagnostic criteria for restless legs syndrome were developed and approved by workshop participants and the executive committee of the International Restless Legs Syndrome Study Group. Criteria were also developed and approved for the additional aforementioned groups.
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              Zinc requirements and the risks and benefits of zinc supplementation.

              Wolfgang Maret, Harold Sandstead (2006)
              The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Children (Basel)
                Journal ID (iso-abbrev): Children (Basel)
                Journal ID (publisher-id): children
                Title: Children
                Publisher: MDPI
                ISSN (Electronic): 2227-9067
                Publication date (Electronic): 29 September 2014
                Publication date Collection: December 2014
                Volume: 1
                Issue: 3
                Pages: 261-279
                Affiliations
                [1 ]University of Arizona, 2800 E. Ajo Way Suite 300, Tucson, AZ 85713, USA
                [2 ]Mercy Children’s Hospital, 621 S. New Ballas Road, Suite 693A, Saint Louis, MO 63141, USA; E-Mail: ujjwal.ramtekkar@ 123456mercy.net
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: avillagomez@ 123456psychiatry.arizona.edu ; Tel.: +1-520-874-2800; Fax: +1-520-874-2796.
                Article
                Publisher ID: children-01-00261
                DOI: 10.3390/children1030261
                PMC ID: 4928738
                PubMed ID: 27417479
                SO-VID: 38a6ff7b-a301-4735-8adf-aa9a1ec421a9
                Copyright statement: © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 31 May 2014
                Date revision received : 12 August 2014
                Date accepted : 21 August 2014
                Categories
                Subject: Review

                Keywords: attention-deficit/hyperactivity disorder,zinc,magnesium,vitamin d,ferritin,iron
                Data availability:
                Keywords: attention-deficit/hyperactivity disorder, zinc, magnesium, vitamin d, ferritin, iron

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